corporate presentation - proactiveinvestors uk€¦ · a brief history of last 12 months… 4...
TRANSCRIPT
Corporate PresentationMarch 2019
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Introduction to Shield Therapeutics
• AIM-listed biotech company (STX.L)
– Market capitalisation ~£77.5m (@15Mar19)
• Primary focus is on developing and commercialising Feraccru®
– A novel oral treatment which is approved in the EU to treat iron deficiency with or without anaemia in adults
– Multiple positive phase 3 clinical trials have confirmed effectiveness
– Out-licensed to Norgine in EU, Australia, New Zealand
– US NDA: PDUFA date 27 July 2019
– Additional late stage asset, PT20, requires one phase 3 study to submit a MAA in Europe and NDA in the USA
• Semi-virtual UK-based company – conduct of clinical trials as well as manufacturing and sales & marketing are out-sourced
– Highly experienced management team
– 15 employees
• Comfortably funded into 2020
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A brief history of last 12 months…
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5Feb18: Initial blinded top-line data from Feraccru® AEGIS-CKD study shows apparent failure to meet primary end-point
27Mar18: EU extends approved Feraccru® indication to all adults with iron deficiency
19Sep18: Feraccru® licensed to Norgine (inc. £11m upfront) for commercialisation in EU, Aus & NZ
13Dec18: FDA accepts Feraccru®
NDA and confirms 27 July 2019 as date for completion of review
16Mar18: AEGIS-CKD detailed analysis shows study did in fact meet primary end-point
Investment proposition – recovery of the business from the consequences of the initial and incorrect AEGIS-CKD study results have not yet been fully reflected in the share price recovery
4Mar19: AEGIS-H2H study shows Feraccru non-inferior to IV iron at treating IDA
Analyst research: Current price targets
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Current shareprice
Iron deficiency and Feraccru®
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Iron deficiency (ID)
• Iron required for multiple vital functions
– Key component of haemoglobin, carrying oxygen from lungs to tissue
– Transport mechanism for electrons within cells
– Facilitating oxygen enzyme reactions
• Iron deficiency occurs when a body either:
– Does not absorb enough iron to supply its needs or,
– Loses iron through blood loss
• ID can be caused by malnutrition, bleeding and a number of chronic diseases, in particular:
– Inflammatory bowel disease (IBD) and
– Chronic kidney disease (CKD)
• Iron deficiency is the most common cause of anaemia (iron deficiency anaemia ‘IDA’)
• ID/IDA is treated with iron replacement therapy
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Anaemia and IDA
• Anaemia is a condition characterised by abnormally low levels of red blood cells or low levels of haemoglobin within red blood cells
• Symptoms of anaemia include:
– Lethargy, fatigue, weakness, depression, impaired immune system, GI disturbances, neuromuscular imbalances
• WHO stages of anaemia:
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Large market: IBD and CKD are increasingly prevalent diseases
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10
20
15
035
EU5
CKD diagnosed prevalence in US, EU5(2017-35F) Millions of patients
US
343332313029282726252421 222019 23182017
1.8%
1.2%
CAGR %
(2017-35F)
Total 1.5%
• Growth in prevalence driven by population growth and underlying proportion of people developing the primary diseases:- IBD rate estimated to be growing at c.1% p.a. in developed nations driven by improved
awareness amongst other factors- CKD rate estimated to be growing at c.1% p.a. in developed nations due to higher levels of
obesity & diabetes plus growth in population >50 yrs old as kidney function declines with age
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10
15
20
0
IBD diagnosed prevalence in US, EU5(2017-35F) Millions of patients
EU5
US
34302621 23 33252218 2719 31 32292017 28 352420
1.7%
1.1%
CAGR %
(2017-35F)
Total 1.4%
c.15 million patients are estimated to have diagnosed IBD or CKD in 2017.
This is expected to grow to c.19 million by 2035
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Iron replacement therapy can be oral or intravenous (IV)
Oral
• Mostly salt-based iron compounds
• Inexpensive and convenient but…
• Poor absorption = slower to restore iron-levels and…
• Not well tolerated = poor compliance
Intravenous
• Used mainly in patients intolerant of oral therapies
• Requires hospital administration due to safety risk
• Resource heavy, inconvenient & costly
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Iron market by volume & value:
Oral
IV
100%
Although oral iron has majority of volume, IV iron has close to 50% of market by value
The tolerability of salt-based oral iron therapies and the cost and inconvenience of IV iron together create a major unmet need and commercial opportunity
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The clear opportunity created by Ferinject®…
Which can now be directly targeted by Feraccru®:Results from the recently reported AEGIS-H2H phase 3b study in ~250 IDA patients showed that:• Feraccru® was non-inferior in responder rate to Ferinject® in treating iron
deficiency anaemia• Feraccru® again showed it was efficiently absorbed & well tolerated over 52 weeks• Feraccru® offers a simple, well tolerated and effective oral treatment alternative to IV
iron therapy without the need for hospital-based administration
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In a market enjoying rapid growth…
Market penetration data for Ferinject® as defined by the amount of iron that is being prescribed per capita suggests that (apart from Switzerland) the ID/IDA markets are in the early stages of development with growth anywhere between 11% and 48% from ’17-’18
Feraccru is a novel oral formulation
• Feraccru® is a low dose oral formulation of a non-salt complex of Fe3+, which is stable in the GI tract
– Other oral irons are salts and require the Fe to dissociate to be absorbed
– This causes formation of insoluble products in the GI tract, causing intolerance in patients
• The Fe3+ in Feraccru® remains in complex with maltol until absorbed and the iron is delivered to the bloodstream where it binds to transferrin
– Maltol gets metabolised and excreted in urine
– Unabsorbed Feraccru® passes through the digestive system in the benign complex and is excreted in faeces
• Feraccru® is a well tolerated oral iron replacement therapy
– Potential for use as a first line treatment for patients with iron deficiency or as an alternative to IV iron in patients failing existing oral iron salts
Source: Shield Therapeutics Investor Materials, 2017; MedScape; EMA; Stallmach et al. 2015; Abbaspour et al. 2014; L.E.K. research
Feraccru® mechanism of action:
Most iron enters
liver and bone
marrow
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Feraccru® in the treatment algorithm
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In
Oral Iron Tolerant
Intravenous (IV) Iron
• Iron directly into the blood• But:
– Potential allergic reactions– Iron overload– Hospital only– Resuscitation team required– Inconvenience and high overall cost
• ID/IDA arises in multiple primary diseases
• Failure to treat leads to lethargy as well as much more serious consequences (e.g. immune & heart complications)
Fe2+
Fe2+
Insoluble complexes
+Radicals
Gut damage side effects
Patient diagnosed with iron deficiency
Oral Iron Intolerant
Up to 70% with gastro side effects
Oral Iron
Key features:✓ Low dose oral iron
✓ Non-inferior to IV iron
✓ Taken twice-daily without food
✓ High iron availability
✓ Effectively raises Hb and iron levels
✓ Well tolerated compared to placebo
✓ No patients in Feraccru long term studies required interventional IV Iron
Feraccru®
• Long patent life• Marketed by Norgine in Europe for the
treatment of iron deficiency in adults• USA NDA process under way, PDUFA
date 27 July 2019
Feraccru® clinical studies
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11
12
13
14
0 4 8 12
Ab
solu
te H
b (
g/d
l)
Duration of treatment (weeks)Feraccru
• Study of 128 IBD patients with IDA
• Patients were intolerant of or unwilling to take oral iron salts
• A clinically relevant haemoglobin (Hb) increase is considered to be 1g/dL
• Feraccru® delivered highly relevant and rapid 2.3g/dL rise inside 12 weeks with 1g/dL in only 4 weeks
P < 0.0001
• Normalised mean Hb by week 12
• Long term compliance levels of 97%
• With chronic therapy patients’ anaemia did not recur and iron indices continued to improve
• Ongoing Feraccru® therapy may prevent need for IV iron
• Majority of adverse events were related to IBD status
• Low incidence of other adverse events
• Neither short or long-term Feraccru® therapy led to iron overload
Source: Marketing Authorisation Application (MAA)
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12
13
14
0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64
Ab
solu
te H
b (
g/d
l)
Weeks of treatment
Normalisation of males
Normalisation of females
010203040506070
% o
f su
bje
cts
Feraccru Placebo
Feraccru provides rapid and effective results...
…works over the long term
Source: Marketing Authorisation Application (MAA)
…and is well-tolerated
Feraccru’s efficacy and safety are key differentiators: AEGIS-IBD
Source: Marketing Authorisation Application (MAA)
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16
AEGIS-CKD Study Analysis (1) (2)
ITT: intention-to-treat; MI: multiple imputations
• Study met primary endpoint of change in Hb from baseline at 16 wks (p = 0.0149)
• Statistically significant change in Hb is observed across all analyses (ITT, mITT and PP) and in all sensitivity analyses at both wk 8 and 16
• Change in ferritin, TSAT and serum iron from baseline statistically significant at weeks 4, 8 and 16 demonstrating early effect
• Hb levels increased and maintained over 52 weeks
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(1) SAP v1.1(2) 169 patients
-0.1
0
0.1
0.2
0.3
0.4
0.5
0.6
Week 4 Week 8 Week 16
Primary endpoint (∆Hb g/dl)
Feraccru Placebo
p=0.0052
p=0.326
p=0.0149
9.5
10
10.5
11
11.5
Week 0 Week 8 Week 16 Week32 Week 42 Week52
Long term follow up (Hb g/dl)
Feraccru armPlacebo armFeraccru (placebo arm)
AEGIS-H2H (Head-to-Head) study
• Feraccru® shown to be non-inferior in responder rate to market-leading intravenous (IV) iron therapy in treating iron deficiency anaemia
• Multi-national Phase IIIb randomised, active-controlled trial in 242 IBD patients with IDA and haemoglobin (Hb) measurements as low as 8.0g/dL
• Compared efficacy and safety of Feraccru® at 12 weeks to IV iron (Ferinject®)
• Efficacy defined as either (i) a 2g/dL rise in Hb from baseline or (ii) Hb normalisation
– Results showed that response to Feraccru® at 12 weeks was well within the 20% limit required by the protocol to confirm non-inferiority (p=0.022) to Ferinject®
• Full data to be submitted for peer-review and subsequent presentation at scientific meetings
• Triggered receipt of €2.5m development milestone from Norgine under the September 2018 licence agreement
• Data will support pricing and reimbursement negotiations
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Europe commercialisationNorgine licence headlines
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Norgine licence headlines
• Exclusive licence to commercialise Feraccru® in Europe*, Australia and New Zealand (announced September 2018)
– £11 million upfront licence payment
– Up to €54.5million in development and sales milestones with €2.5million development milestone triggered by AEGIS-H2H results
– Royalties ranging from 25% to 40% as sales increase
• Why Norgine? It is a well-resourced, European-focused specialty pharma business with a proven commercial track record for whom Feraccru® is a central product for growth
– Commercial operations now active in the UK and Germany, with >80 field-based staff promoting and supporting Feraccru®
• Shield globally responsible for:
– Manufacture and supply of Feraccru®
– All aspects of current and future development
– All aspects of intellectual property
• Shield also retains full commercial rights to Feraccru® in all unlicensed countries including the USA
* Excluding countries covered by AOP (Scandinavia) and EWO (Switzerland)
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USA
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USA
• September 2018: NDA for Feraccru® submitted
• December 2018: FDA accepted Feraccru® NDA for review
• December 2018: PDUFA date (completion of review) confirmed as 27 July 2019
• Shield now considering commercialisation options for Feraccru® in the USA, most likely to out-license
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Financial headlines
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Financial position
• Revenues of £11.9m* in 2018
– £11m upfront payment from Norgine to licence Feraccru® in the EU
– £0.9m of Feraccru® revenue (sales + royalties) despite the product being commercially unsupported since February 2018
– Feraccru® demonstrated quarter on quarter growth of ‘in market’ sales through 2018
• Cash balance of £9.8m* at year end
• €2.5m development milestone received from Norgine following AEGIS-H2H results
• Cash runway extends comfortably into 2020
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* Unaudited results
Newsflow and investment highlights
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Anticipated 2019 newsflow
Indicative timing Event
27 July 2019 PDUFA date for US approval of Feraccru®
H2 2019 Start of Paediatric Phase III study
Ongoing/ad hoc Potential further out-licensing agreements for Feraccru® in USA and other territories
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Takeaway messages & investment highlights
• Shield Therapeutics is a highly-focused, commercial stage, specialty medicines business– Iron deficiency with or without anaemia - the indication for our lead product, Feraccru® - is a rapidly
growing market worth >$2bn pa, yet the market is poorly penetrated and patients clearly have an ongoing unmet medical need that Feraccru® may resolve
• Feraccru®– A novel oral ferric iron therapy with efficacy & safety proven across a range of clinical trials inc. in
comparison to Ferinject®, the leading IV iron product
– Approved in Europe for the treatment of iron deficiency with or without anaemia in adults
– Actively promoted by Norgine, a proven European-focused commercial organisation
– Feraccru® NDA decision due 27 July 2019 potentially giving approval in the world’s largest and most attractive pharma market
• Cash runway comfortably extends into 2020– Recent positive AEGIS-H2H study led to a €2.5m payment from Norgine
• Valuation upside– Feraccru® has a large and growing market opportunity enhanced by recent positive results of a head to
head study of Feraccru versus IV iron
– US approval is on the horizon and markets like the USA, China and Japan are available for licensing
– PT20 only requires one additional phase 3 study prior to regulatory submission and is available for licensing in all markets
– However:• Shield’s market capitalisation is only £77m as of 15 Mar 19
• Current consensus analyst valuation1 - £130m (116p/share), ranging up to £179m (153p/share)
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1 Peel Hunt, Liberum, Edison, Capital Networks
Management team
Name Role Biography
Carl Sterritt
CEO & Founder Started Shield Therapeutics in 2008 and identified the Feraccru opportunity in 2010. Previously held senior management roles at United Therapeutics and EncysivePharmaceuticals, working on innovative therapies for the treatment of pulmonary arterial hypertension; founding the Group after Encysive was acquired by Pfizer Inc
Tim Watts Chief Financial Officer Tim joined the company as Interim Chief Financial Officer in August 2018 and has over 25 years’ experience in the pharmaceutical and biotech sectors. A chartered accountant, he was Group Financial Controller of AstraZeneca plc (2002-2006), CFO of Archimedes Pharma (2007-2011) and CFO of Oxford Biomedica plc (2012-2017)
Mark Sampson
Chief Medical Officer Having joined in 2015, Mark has more than 25 years of pharmaceutical development and commercialisation experience at companies such as SmithKline Beecham, Amgen and Gilead. Before entering into the pharmaceutical industry Mark qualified and practised as a surgeon in the NHS
Jackie Mitchell
VP, Regulatory Affairs and Quality
With over 20 years’ experience in regulatory affairs Jackie has led the group’s regulatory activities since 2012. She has led several major regulatory projects, including successful MAA and NDA submissions, including MAAs for the Feraccru, Kaletra and Humira.
David Childs
Director, Product Supply & Commercial Alliances
David joined in 2011 as Director of Manufacturing. During his tenure at GSK, David gained over 18 years’ of experience in chemical and pharmaceutical development and worked closely with several outsourcing partners.
Lucy Bailey General Counsel & Company Secretary
Lucy has worked with Shield since 2015 and was a key member of the team working on the admission of Shield Therapeutics to the AIM market in 2016. She is admitted as a Solicitor of the Senior Courts of England and Wales and has worked previously at both a boutique and an international US law firm based in Singapore
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AEGIS-CKD Study: the story of Feb-Mar 2018
• A pivotal Phase III study with primary endpoint evaluating haemoglobin response to Feraccru® after 16 weeks compared with placebo, in patients with pre-dialysis chronic kidney disease (CKD)
• Initial blinded top-line data suggested that Feraccru® had failed to meet primary endpoint
• Detailed investigation identified a number of patients who experienced pre-defined events after week 8 that led to withdrawal but, as permitted in the study protocol, week 16 endpoint data was collected which confounded the blinded analysis e.g.
– Placebo patients receiving blood transfusions & Feraccru® patients suffering non-related bleeds
• Full analyses using the pre-specified statistical analysis plan, using “last observation carried forward” methodology as agreed with regulators, corrected for the confounding data
• Study showed that patients treated with Feraccru® demonstrated a highly statistically significant response (p=0.0149) in haemoglobin levels after 16 weeks of treatment compared to placebo
• Furthermore
– A highly statistically significant response (p=0.0052) in haemoglobin levels compared to placebo was already seen after just 8 weeks of treatment
– Ferritin levels (key marker of iron absorption) increased significantly compared to placebo at 4, 8 and 16 weeks (p=0.0004)
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Other Feraccru® studies
AEGIS-PAED PK Phase I Pharmacokinetics study:
• Top-line data reported June 2018
• 36 subjects aged 12-17 years
• Feraccru® achieved all pre-defined goals including positive effects on serum parameters and good tolerance at all dosing levels
Phase III paediatric study:
• Expected to start recruitment H2 2019
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